Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer’s disease
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Cardiorespiratory fitness (CRF) is an objective measure of habitual physical activity (PA), and has been linked to increased brain structure and cognition. The gold standard method for measuring CRF is graded exercise testing (GXT), but GXT is not feasible in many settings. The objective of this study was to examine whether a non-exercise estimate of CRF is related to gray matter (GM) volumes, white matter hyperintensities (WMH), cognition, objective and subjective memory function, and mood in a middle-aged cohort at risk for Alzheimer’s disease (AD). Three hundred and fifteen cognitively healthy adults (mean age =58.58 years) enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent structural MRI scanning, cognitive testing, anthropometric assessment, venipuncture for laboratory tests, and completed a self-reported PA questionnaire. A subset (n = 85) underwent maximal GXT. CRF was estimated using a previously validated equation incorporating sex, age, body-mass index, resting heart rate, and self-reported PA. Results indicated that the CRF estimate was significantly associated with GXT-derived peak oxygen consumption, validating its use as a non-exercise CRF measure in our sample. Support for this finding was seen in significant associations between the CRF estimate and several cardiovascular risk factors. Higher CRF was associated with greater GM volumes in several AD-relevant brain regions including the hippocampus, amygdala, precuneus, supramarginal gyrus, and rostral middle frontal gyrus. Increased CRF was also associated with lower WMH and better cognitive performance in Verbal Learning & Memory, Speed & Flexibility, and Visuospatial Ability. Lastly, CRF was negatively correlated with self- and informant-reported memory complaints, and depressive symptoms. Together, these findings suggest that habitual participation in physical activity may provide protection for brain structure and cognitive function, thereby decreasing future risk for AD.
KeywordsCardiorespiratory fitness Preclinical Alzheimer’s disease MRI White matter hyperintensities Cognition Mood
This work was supported by National Institute on Aging grants K23 AG045957 (OCO), R01 AG027161 (MAS), R01 AG021155 (SCJ), P50 AG033514 (SA), and P50 AG033514-S1 (OCO); by a Veterans Administration Merit Review Grant I01CX000165 (SCJ); and by a Clinical and Translational Science Award (UL1RR025011) to the University of Wisconsin, Madison. Portions of this research were supported by the Wisconsin Alumni Research Foundation, the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, and from the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI.
Special thanks to James H. Stein, MD, Claudia Korcarz, DVM RDCS, Jean Einerson, MS, Jessica Horn, BS CEP, and the rest of the Artherosclerosis Imaging Research Program for facilitating graded exercise tests; Caitlin A. Cleary, BS, Sandra Harding, MS, Jennifer Bond, BA, Janet Rowley, BA, and the WRAP psychometrists for helping with study data collection; researchers and staff at the Waisman Center, University of Wisconsin–Madison, where the brain scans took place; and participants in the Wisconsin Registry for Alzheimer’s Prevention for their continued dedication.
Elizabeth A. Boots, Stephanie A. Schultz, Jennifer M. Oh, Jordan Larson, Dorothy Edwards, Dane Cook, Rebecca L. Koscik, Maritza N. Dowling, Catherine L. Gallagher, Cynthia M. Carlsson, Howard A. Rowley, Barbara B. Bendlin, Asenath LaRue, Sanjay Asthana, Bruce P. Hermann, Mark A. Sager, Sterling C. Johnson, and Ozioma C. Okonkwo declare no conflicts of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.
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